This invention relates to a new method for the synthesis of 2,3,5-trisubstituted-2-cyclopentenones. In particular, the invention relates to such a method using a base induced cyclization.
2,3,5-trisubstituted-2-cyclopenteones (and 2,3-disubstituted-2-cyclopentenones) are useful as fragrances and as pharmaceutical intermediates. For instance, 2-(cis-2-pentenyl)-3-methyl-2-cyclopentenone, commonly known as cis-jasmone, and 2-pentyl-3-methyl-2-cyclopentenone, commonly known as dihydrojasmone, are expensive perfume ingredients, and 2,3-dimethyl-2-cyclopentenone is an intermediate useful in the synthesis of the antibiotic methylenomycin B.
2,3,5-trisubstituted-2-cyclopentenones have been prepared by the intramolecular base catalyzed aldolcondensation of acyclic 1,4-dicarbonyl compounds (R. A. Ellison, Synthesis, 1973, 397; M. Mikolajcayk, S. Grzejsczak, and K. Korbacz, Tetrahedron Lett., 22, 3097 (1981); M. Miklojczyk, S. Grzejsczak, and P. Kyzawa, Tetrahedron Lett., 23, 2237 (1982); J. L. Herrman, J. E. Richmann, and R. H. Schlessinger, Tetrahedron Lett., 35, 3275 (1973); P. Bakuzis and M. L. F. Bakuzis, J. Org. chem. 42, 2362 (1977); S. C. Subramaniam, P. J. Thomas, V. R. Mamdapur, and M. S. Chadha, J. Chem. Soc. Perkin 1, 2346 (1979)), and by an intramolecular Wittig reaction effected by the treatment of the anion of .alpha.-diketones with vinyl triphenyl phosphonium salts (A. G. Cameron and A. T. Hewson, J. Chem. Soc. Perkin. Trans. 1, 2979 (1983); I. Kawamoto, S. Muramatsu, and Y. Yura, Tetrahedron Lett. 48, 4223 (1974)). Other routes based on dioxocyclopentanes (Y. Yura and J. Ide, Chem. Pharm. Bull, 17, 408 (1969)), cyclopentane-1,2-diones (J. L. E. Erickson and F. E. Collins, Jr., J. Org. Chem. 30, 1050 (1965)) and cyclodehydration of .gamma.-lactones (K. Sisido, S. Torji, and M. Kawanisi, J. Org. Chem., 29, 904 (1964)), but these routes tend to be either very lengthy or involve the use of very expensive reagents. Other routes include (G. Buchi and B. Egger, J. Org. Chem., 26, 2021 (1971); S. C. Welch, J. N. Assercq, J. P. Loh, and S. A. Glase, J. Org. Chem., 52, 1440 (1987); P. Grieco, J. Org. Chem., Vol. 37, No. 14, (1972) p. 2363-2364; and T. Mukaiyama, J. Am. Chem. Soc., 94:24 (1972) p. 8641-8642).